Data_Sheet_1_Molecular and Functional Profiles of Exosomes From HPV(+) and HPV(−) Head and Neck Cancer Cell Lines.DOCX

Exosomes produced by tumor cells have been shown to reprogram functions of human immune cells. Molecular cargos of exosomes isolated from supernatants of HPV(+) and HPV(−) head and neck cancer (HNC) cell lines or from HNC patients' plasma were compared. The exosome protein profiles resembled those of respective parent tumor cells. Only HPV(+) exosomes carried E6/E7, p16, and survivin. HPV(−) exosomes were negative for cyclin D1 and carried low p53 levels. Immunomodulatory molecules (TGF-β, FasL, OX40, OX40L, and HSP70) were carried by HPV(+) and HPV(−) exosomes. These exosomes co-incubated with human T cells induced apoptosis and suppressed T cell activation and proliferation. HPV(−) exosomes suppressed DC maturation and expression of antigen processing machinery (APM) components. In contrast, HPV(+) exosomes promoted DC maturation and did not suppress expression of APM components in mature DCs. While DCs readily internalized exosomes, T lymphocytes resisted their uptake during the initial 12 h co-culture. Thus, HPV(+) exosomes capable of sustaining DC functions may play a key role in promoting anti-tumor immune responses thereby improving outcome in patients with HPV(+) cancers.

肿瘤细胞产生的外泌体已被证实能够重新编程人体免疫细胞的功能。从HPV(+)和HPV(−)头颈部癌细胞系的上清液或头颈部癌症患者血浆中分离的外泌体的分子载荷进行了比较。外泌体蛋白质谱与相应的亲本肿瘤细胞相似。仅HPV(+)外泌体携带E6/E7、p16和survivin。HPV(−)外泌体对cyclin D1呈阴性，并携带低水平的p53。免疫调节分子（TGF-β、FasL、OX40、OX40L和HSP70）被HPV(+)和HPV(−)外泌体携带。这些外泌体与人类T细胞共孵育可诱导细胞凋亡并抑制T细胞的活化和增殖。HPV(−)外泌体抑制DC成熟和抗原处理机制（APM）组分的表达。相反，HPV(+)外泌体促进DC成熟，并不抑制成熟DCs中APM组分的表达。尽管DCs易于摄取外泌体，T淋巴细胞在初始12小时共培养期间对其摄取具有抵抗力。因此，能够维持DC功能的HPV(+)外泌体可能在促进抗肿瘤免疫反应中发挥关键作用，从而改善HPV(+)癌症患者的预后。